Senile dementia of the Alzheimer Type (SDAT) is a clinical entity that afflicts over one million Americans. Its hallmark symptom is cognitive dysfunction, especially in memory processes, and its etiology appears to include a cholinergic-specific loss of neurons in the nucleus basalis of Meynert and decreased cholinergic activity in the hippocampus. Since contemporary medical treatments fail to markedly aid patients with SDAT, alternative methodologies, beginning with animal models of SDAT, need to be investigated. The present proposal aims to evaluate the effectiveness of transplantation of different types of cholinergic neurons in restoring cognitive function lost following septohippocampal lesions. Prior investigations have demonstrated that grafts of fetal septal tissue partially restore T-maze performance following septohippocampal lesions in rodents. Since septal tissue only partially alleviates cognitive deficits and the use of fetal tissue has both biological and social limitations for improving the human condition, other types of donor material will be employed to assess their effectiveness in restoring lost function. Septohippocampal (fimbria-fornix) or sham lesioned rats will receive transplants of one of the following donor materials: 1) fetal septal tissue, 2) peripheral cholinergic tissue (submandibular ganglia), 3) acetylecholine producing neuroblastoma cells that have been rendered amitotic, 4) a control tissue transplant, or 5) no transplant. They will then be tested on the T-maze, a task of representational memory, using a reward alternation paradigm. Following behavioral testing, rats will be sacrificed and undergo histological procedures for lesion verification, acetylecholinesterase staining, and autoradiography, to correlate behavioral findings with cholinergic reinnervation. While the present study does not use nonhuman primates, our research group feels strongly that the most relevant experiments require animals with nervous systems more closely resembling the human brain than is found in rodents. Accordingly we are committed to developing nonhuman primate models of human neurological dysfunctions like SDAT and the present study will serve as a base to initiate future experiments on neural transplants into monkeys with cognitive disorders.